Does the immune system of a mouse age faster than the immune system of a human?

One of the characteristics of all somatic cells is a finite life span. Cells may proliferate until they reach a point after which, although they are metabolically active, they can no longer produce daughter cells. This observation is central to the clonal exhaustion hypothesis, a mechanism cited to explain age-associated immune dysfunction. In this hypothesis, repeated division of lymphocytes leads to a replicative limit, after which they enter the senescent phase but are not lost from the pool of T cells. Advancing age would then be associated with an increase in the number of T cells that are unable to proliferate to a stimulus which induces a proliferative response in T cells from younger individuals. This hypothesis seems both logical and reasonable and is supported by data from both humans and mice with the demonstration of an age-related accumulation of senescent T cells in both species. However, there is an apparent paradox. The paradox arises because the onset of immunosenescence appears to be more closely linked to the life span of the animal rather than the life span of the lymphocyte. BioEssays 21:519–524, 1999. © 1999 John Wiley & Sons, Inc.     

Therapeutic imprinting of the immune system: towards a remission of AIDS in primates?

This correspondence was written in response to the comments by Young et al. Following careful evaluation of the relevant dataset, each of the points brought up by Young et al. has been addressed in this response. We anticipate this will clarify our findings regarding ERV_mch8, an ecotropic endogenous retrovirus that was shown to have cerebellum-specific and age-dependent expression patterns in C57BL/6J mice.     

Response of the dung beetle community to different climatic zones: Does the land use system matter?

The conversion of Brazilian savanna into exotic pastures leads to the loss of dung beetles and a decrease in their contribution to ecological functions. We hypothesized that the dung beetle communities from exotic pastures would show greater significant differences between climatic zones, when contrasted to communities from Brazilian savanna in the same region, since dung beetle assemblages in pastures are more simplified. We assessed which variables (purpose of production, type of management, percentage the habitat per buffer, soil penetration resistance, pasture area and herd size) affect more the dung beetle community in exotic pastures. We carried out this study in 48 areas of native Brazilian savannas and exotic pastures distributed across four bioclimatic zones: BZ1, hot with three dry months; BZ2, hot with 4–5 dry months; BZ3, sub-hot with 4–5 dry months and BZ4, meso-thermal with 4–5 dry months of Minas Gerais State, Brazil. In each BZ, six areas of Brazilian savannas and six areas of exotic pasture were selected. In the Brazilian savanna areas, the species richness, abundance and biomass of dung beetles did not differ between the bioclimatic zones, unlike the exotic pastures. The composition of the dung beetle community was different between land use systems and between bioclimatic zones; the interaction between the two factors was also significant. Our results provide evidence that dung beetle communities active in exotic pastures are more susceptible to climatic environmental variations than communities from more complex and stable habitats, such as savannas. Finally, the best model suggested that all the six variables combined explained about 91% of the total variability in species composition observed between sampling sites.     

Does it matter who pulls the switch? Perceptions of intentions in the trolley dilemma

This research examines the automatic moral and intentional inferences that third parties generate as a function of outcomes for the actor. Participants were asked about the moral acceptability of redirecting a train to save five lives by sacrificing one, as well as the intentions of the person directing the train, and the consequences of doing so. Actor position was varied with respect to whether the person redirecting the train stood to benefit by doing so. Across four studies in international and US samples, participants rated the redirection as less morally acceptable or more punishable when the actor redirecting the train was saving their own life in the process. The implications of these findings for moral claims are discussed.     

Therapeutic effects of metformin in breast cancer: involvement of the immune system?

Breast cancer and associated diabetes mellitus have gained raising interest as an elevated risk of breast cancer prognosis resulting in increased mortality in diabetic patients. In this context, the long-acting insulin analog glargine and other antidiabetics have been discussed to promote tumorigenesis. In contrast, the biguanide class oral antidiabetic metformin has been shown capable of enhancing cell cycle arrest and inducing apoptosis as well as reducing growth factor signaling. Consequently, several studies are underway to evaluate a possible role of metformin in breast cancer treatment. Although mechanisms involved are not definitely clear yet, here, we discuss metformin’s anticancer effects including the potential impact of the immune system.     

Evolution of the mammary gland from the innate immune system?

The mammary gland is a skin gland unique to the class Mammalia. Despite a growing molecular and histological understanding of the development and physiology of the mammary gland, its functional and morphological origins have remained speculative. Numerous theories on the origin of the mammary gland and lactation exist. The purpose of the mammary gland is to provide the newborn with copious amounts of milk, a unique body fluid that has a dual role of nutrition and immunological protection. Interestingly, antimicrobial enzymes, such as xanthine oxidoreductase or lysozyme, are directly involved in the evolution of the nutritional aspect of milk. We outline that xanthine oxidoreductase evolved a dual role in the mammary gland and hence provide new evidence supporting the hypothesis that the nutritional function of the milk evolved subsequent to its protective function. Therefore, we postulate that the mammary gland evolved from the innate immune system. In addition, we suggest that lactation partly evolved as an inflammatory response to tissue damage and infection, and discuss the observation that the two signaling pathways, NF-kB and Jak/Stat, play central roles in inflammation as well as in lactation.     

Sexually-transmitted disease in a sub-tropical eucalypt beetle: infection of the fittest?

The ecology of sexually-transmitted diseases (STDs) is topical in scientific research, and their demography and epidemiology differ from those of classical pathogens and parasites. Transmission of STDs is generally density-independent, occurs via the “fittest” individuals in a population (or, at least, those that achieve the most matings), and reflects differential mating success. STDs can therefore have a major influence on the evolution of host mating systems. We studied the epidemiology of a recently described STD of a chrysomelid beetle in applied and theoretical contexts, exploring the virulence, intensity and prevalence of infection, and using our results to test ecological predictions. Chrysophtharta cloelia is infected with a sexually-transmitted mite (the STD), Parobia captivus. Infection rate over three beetle generations (7 months) was determined and the STD’s effects on fertility, fecundity, longevity, mating success and overwintering survival was measured. Throughout the season around 40% of beetles were infected, with approximately one quarter of such hosts carrying infective life stages of the STD at any one time. Infection by P. captivus significantly decreased overwintering survival, but did not impact on other fitness parameters measured, including mate acceptance. However, more female beetles were infected than male beetles, while within both sexes larger beetles were more likely to be infected. Our results concur with theoretical predictions that STDs may be selected for low virulence and low detectability, while the observation of female bias in infection supports hypotheses regarding variable mating success and mating skews, which we discuss.     

The liver: an organ of the immune system?

The liver stands in a unique position between the gastrointestinal tract and systemic venous system. Its constant exposure to food antigens, bacterial products and potential pathogens through the mesenteric circulation, requires the liver to maintain tolerogenic capabilities while preserving the means to mount effective immune responses. The liver has the unique ability amongst solid organs, to activate na?ve CD8+ T lymphocytes in an antigen-specific manner. However, this activation can be inefficient and lead to apoptosis. This phenomenon is believed to be involved in both, the development of oral tolerance and the induction of tolerance in liver allografts. The liver is the target of both autoimmune diseases and of chronic viral infections and its unique tolerogenic environment has frequently been suggested as a factor in the development of these diseases. A better grasp of the liver's unique immunological processes would lead to a better understanding of immune tolerance mechanisms and their role in the development of autoimmune diseases and chronic viral infections.     

Eurasian lynx hunting red deer: is there an influence of a winter enclosure system?

As in several Central European areas, in the Bohemian Forest Ecosystem (Germany and the Czech Republic), fenced feeding enclosures are used for the winter management of red deer (Cervus elaphus), which is an important component of the Eurasian lynx’s (Lynx lynx) winter diet. Using GPS telemetry data, we tested whether (1) lynx hunted red deer mainly selecting for high prey densities and environmental characteristics like a good level of habitat heterogeneity, independently of the enclosures’ presence; (2) enclosures attracted lynx and (3) positively influenced their predation on red deer, being predictable and abundant prey sources throughout the winter; or (4) extremely high deer densities inside the enclosures rather negatively influenced lynx predation on this species. We first compared lynx space usage and predation on red deer inside and outside the enclosures. Then, we investigated the effects of the environment, prey densities and the enclosure distance for the area outside of enclosures. Prey densities positively influenced lynx space usage, whilst the probability of predation on red deer was highest at medium to low red deer densities. Habitat heterogeneity and terrain ruggedness influenced both lynx space usage and probability of predation on red deer. Regarding the effect of enclosures, the ratio “area used during night vs. daytime” was larger by a factor of 2 inside compared to outside enclosures, and the probability of predation on red deer was three times higher inside rather than outside of enclosures; however, these differences were not statistically significant, suggesting that the influence of the enclosures is not very pronounced.     

What is the role of endothelin system?

Endothelins are a family of three peptides of 21 amino acids with strong vasoconstrictor effects. The three peptides are encoded by three different genes and derived from precursors (" big endothelins") which are cleaved by metalloproteases, named endothelin-converting enzyme. Two receptors have been cloned, ET-A and ET-B which bind the three endothelins with various affinities. The diverse expression pattern of the endothelin system (ET) components is associated with a complex pharmacology and its counteracting physiological actions. New modulators of the ET system have been described : retinoic acid, leptin, prostaglandins, hypoxia. Endothelins can be considered as regulators working in paracrine and autocrine fashion in a variety of organs in different cellular types. The ET system has beneficial and detrimental roles in mammals. The different components have been shown to be essential for a normal embryonic and neonatal development, for renal homeostasis and maintenance of basal vascular tone. They are involved in physiological and tumoral angiogenesis. They affect the physiology and pathophysiology of the liver, muscle, skin, adipose tissue and reproductive tract. The endothelin system participates in the development of atherosclerosis as well as pulmonary hypertension, and mediates cardiac remodeling in heart failure. Elaboration of new animal models (knock-out, pathophysiological models em leader ) will allow the clear genetic dissection of physiological and pathophysiological roles of the endothelin system.     

Cadherins and the cortex: A matter of time?

Cell adhesion systems commonly operate in close partnership with the cytoskeleton. Adhesion receptors bind to the cortex and regulate its dynamics, organization and mechanics; conversely, the cytoskeleton influences aspects of adhesion, including strength, stability and ductility. In this review we consider recent advances in elucidating such cooperation, focusing on interactions between classical cadherins and actomyosin. The evidence presents an apparent paradox. Molecular mechanisms of mechanosensation by the cadherin-actin apparatus imply that adhesion strengthens under tension. However, this does not always translate to the broader setting of confluent tissues, where increases in fluctuations of tension can promote intercalation due to the shrinkage of adherens junctions. Emerging evidence suggests that understanding of timescales may be important in resolving this issue, but that further work is needed to understand the role of adhesive strengthening across scales.     

Taking care of patients--does it matter whether the physician is a woman?

Researchers have recently begun to compare male and female physicians'' attitudes toward patients, medical knowledge, and practice styles. Although women start medical school with more "humanistic views," the conservative effect of medical socialization on both male and female students attenuates these differences. While some studies suggested that men are more scientifically knowledgeable, recent studies showed no significant differences in physicians'' medical knowledge. Male and female physicians also had comparable diagnostic and therapeutic behavior. In the intimate world of physicians and patients, however, there were notable differences. Women physicians seemed better able to communicate sensitivity and caring to patients, which may account for the common perception that women are more caring and empathic physicians. Medical educators may wish to study more closely female physicians'' communication styles to identify these behaviors and inculcate them into all physicians.     

Obesity and the rate of time preference: is there a connection?

It is hypothesized that recent trends in US and worldwide obesity are, in part, related to an increase in the marginal rate of time preference, where time preference refers to the rate at which people are willing to trade current benefit for future benefit. The higher the rate of time preference, the larger is the factor by which individuals discount the future health risks associated with current consumption. Data from the United States, as well as international evidence, suggest that a relationship between these two variables is plausible. The authors encourage researchers to explore the possible link between obesity and time preference, as important insights are likely to result.     

Condensed tannins in the diets of primates: a matter of methods?

To understand the ways in which condensed tannins (CT) affect primate diet selection and nutritional status, correct measurements are essential. In the majority of studies of the CT contents of primate foods, a tannin source such as "quebracho" is used to standardize CT assays, but the CT in quebracho tannin may not be similar to those in the plants of interest. We investigated how the choice of standard to calibrate CT assays affects the estimation of CT in the diets of mountain gorillas (Gorilla beringei). We purified the CT from gorilla foods and compared the actual amounts of CT in the foods with estimates produced by using the quebracho tannin. When quebracho was used, the estimates of CT contents of gorilla foods were, on average, 3.6 times the actual content of CT so that the amounts in frequently eaten gorilla foods were substantially overestimated. The overestimation for a given plant could not be predicted reliably and the ranking of plants by tannin content differed according to the standard used. Our results demonstrate that accurate measurements of CT necessitate the use of tannins purified from the plant species of interest. A reevaluation of primatology studies using interspecific comparisons of tannin content will provide new insights into primate food selection and nutritional ecology.     

Hamsters running on time: is the lateral habenula a part of the clock?

Previous anatomical and physiological studies have implicated the lateral habenula, and especially its medial division (LHbM), as a candidate component of the circadian timing system in rodents. We assayed lateral habenula rhythmicity in rodents using c-FOS immunohistochemistry and found a robust rhythm in immunoreactive cell counts in the LHbM, with higher counts during the dark phase of a light-dark (LD) cycle and during subjective night in constant darkness. We have also observed an obvious asymmetry of c-FOS expression in the LHbM of behaviorally "split" hamsters in constant light, but only during their active phase (when they were running in wheels). Locomotor activity rhythms appear to be regulated by the suprachiasmatic nucleus (SCN) via multiple output pathways, one of which might be diffusible while the other might be neural, involving the lateral habenula.